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Macrophages and progressive tubulointerstitial disease

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Presentation on theme: "Macrophages and progressive tubulointerstitial disease"— Presentation transcript:

1 Macrophages and progressive tubulointerstitial disease
Kevin Sean Eardley, Paul Cockwell  Kidney International  Volume 68, Issue 2, Pages (August 2005) DOI: /j x Copyright © 2005 International Society of Nephrology Terms and Conditions

2 Figure 1 Secretory products of activated interstitial macrophages that may promote tubular atrophy, scar formation, and peritubular capillary loss in secondary tubulointerstitial disease.. Kidney International  , DOI: ( /j x) Copyright © 2005 International Society of Nephrology Terms and Conditions

3 Figure 2 An overview of monocyte trafficking: (1) selectin-mediated rolling of the leukocyte rolling on the EC surface; (2) integrin-mediated firm adhesion to EC surface; (3) integrin-mediated spreading and migration to the EC junction; (4) integrin, PECAM-1, CD99, and JAM-1-mediated diapedesis. Chemokines immobilized at the EC or in solution have a biological role at each step. Kidney International  , DOI: ( /j x) Copyright © 2005 International Society of Nephrology Terms and Conditions

4 Figure 3 Dual staining IHC demonstrating (A) CD68+ve macrophages, (B) CD3+ve T cells, and (C) their colocalization, in the interstitium in advanced ischemic nephropathy (×400). The methodology utilized the 3-step indirect IHC technique on serial sections, initially staining for anti-CD68 (5 μg/mL; clone PG-M1; Dako, Ltd., Ely, UK) and visualizing with DAB (brown pigment), followed by staining for anti-CD3 (30 μg/mL clone UCHT-1; Dako) and visualizing with Fast Blue (blue pigment) (C). The controls used were serial sections with the replacement of either the first (B), second (A), or both (D) antibodies with an isotype control at the identical concentration. (E and F) Immunohistochemistry demonstrating MCP-1/CCL2 expression in advanced IgA nephropathy (×400). MCP-1/CCL2 is expressed predominantly by tubular epithelial expression in chronic nonproliferative nephropathies. There is no glomerular tuft (*) expression, and little glomerular epithelial expression (arrow) [anti-MCP-1; AF-279-NA; 10 μg/mL; R&D Systems, UK (E); isotype (F)]. (G and H) Dual staining IHC demonstrating CCR2 expression by interstitial macrophages in membranous nephropathy. CCR2 expression [anti-CCR2; clone 5A11; 20 μg/mL; gift from LeukoSite, Cambridge, MA; DAB (brown) visualization] (G and H) colocalizes with CD68 expression (Blue, Fast Blue visualization) to produce black color (arrows) (H). Methodologies as described for 3A-D. Studies performed by K. E. Kidney International  , DOI: ( /j x) Copyright © 2005 International Society of Nephrology Terms and Conditions

5 Figure 4 Proteinuria theory. Schemata of mechanisms by which proteinuria promotes Mφ recruitment to the interstitium. Kidney International  , DOI: ( /j x) Copyright © 2005 International Society of Nephrology Terms and Conditions

6 Figure 5 Hypoxia theory. Schemata of mechanisms by which hypoxia promotes Mφ recruitment to the tubulointerstitium, which, in turn, exacerbates tissue hypoxia. Kidney International  , DOI: ( /j x) Copyright © 2005 International Society of Nephrology Terms and Conditions

7 Figure 6 Glomerular cytokine theory. Schemata of the 4 mechanisms by which glomerular-derived cytokines reach the tubulointerstitium, where they may then promote Mφ recruitment (see text). Kidney International  , DOI: ( /j x) Copyright © 2005 International Society of Nephrology Terms and Conditions


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